Xiang Yan, Zhang Meiling, Wang Qian, Liu Jingwen, Zeng Lulin, Sun Ao, Lu Kaihua
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Curr Oncol. 2025 Mar 4;32(3):148. doi: 10.3390/curroncol32030148.
HER2 mutations are rare driver events in advanced NSCLC, with limited relief from current targeted therapies. This study aimed to characterize the molecular features of HER2-mutant NSCLC and to evaluate the clinical efficacy of pyrotinib-based combination therapy as a first-line treatment, providing evidence for optimizing treatment strategies. NSCLC patients diagnosed at Jiangsu Province People's Hospital from 2016 to 2024 were enrolled. HER2-positive cases were screened by IHC/FISH and further profiled by NGS. Treatment response was assessed by RECIST 1.1, and survival analysis was performed using Kaplan-Meier and log-rank tests. Among 144 HER2-mutant NSCLC cases confirmed by NGS, 10 insertion mutations, 26 missense mutations, and 2 fusion mutations were identified. The most common mutation was the exon 20 p.A775_G776insYVMA (47.9%), and TP53 was the most frequent co-mutation (10.4%). In terms of efficacy, the pyrotinib-based combination therapy demonstrated significant clinical benefit, with an ORR of 33.3%, DCR of 95.2%, median PFS (mPFS) of 11.3 months (95% CI: 10.27-12.26), and median OS (mOS) of 21.0 months (95% CI: 18.00-23.94). Subgroup analysis revealed no significant impact of mutation subtype or co-mutation status on the treatment efficacy, but patients with brain metastases had a significantly worse prognosis than those without metastasis (mPFS: 5.1 vs. 12.9 months, < 0.01; mOS: 9.3 vs. 26.5 months, < 0.01). All TRAEs were grade 1-3 (any grade: 90.5%; grade 3: 14.3%), with the most common TRAE being diarrhea (any grade: 85.7%; grade 3: 9.5%). Pyrotinib-based combination therapy is a feasible first-line treatment for HER2-mutant NSCLC, demonstrating significant survival benefits and manageable toxicity. However, brain metastasis patients require enhanced comprehensive management.
HER2突变是晚期非小细胞肺癌（NSCLC）中罕见的驱动事件，目前的靶向治疗缓解有限。本研究旨在表征HER2突变型NSCLC的分子特征，并评估以吡咯替尼为基础的联合治疗作为一线治疗的临床疗效，为优化治疗策略提供依据。纳入了2016年至2024年在江苏省人民医院确诊的NSCLC患者。通过免疫组化/荧光原位杂交（IHC/FISH）筛选HER2阳性病例，并通过二代测序（NGS）进一步分析。根据实体瘤疗效评价标准（RECIST）1.1评估治疗反应，并使用Kaplan-Meier法和对数秩检验进行生存分析。在144例经NGS确诊的HER2突变型NSCLC病例中，鉴定出10例插入突变、26例错义突变和2例融合突变。最常见的突变是外显子20的p.A775_G776insYVMA（47.9%），TP53是最常见的共突变（10.4%）。在疗效方面，以吡咯替尼为基础的联合治疗显示出显著的临床获益，客观缓解率（ORR）为33.3%，疾病控制率（DCR）为95.2%，中位无进展生存期（mPFS）为11.3个月（95%置信区间：10.27-12.26），中位总生存期（mOS）为21.0个月（95%置信区间：18.00-23.94）。亚组分析显示，突变亚型或共突变状态对治疗疗效无显著影响，但有脑转移的患者预后明显差于无转移的患者（mPFS：5.1个月对12.9个月，<0.01；mOS：9.3个月对26.5个月，<0.01）。所有治疗相关不良反应（TRAEs）均为1-3级（任何级别：90.5%；3级：14.3%），最常见的TRAEs是腹泻（任何级别：85.7%；3级：9.5%）。以吡咯替尼为基础的联合治疗是HER2突变型NSCLC可行的一线治疗方案，显示出显著的生存获益且毒性可控。然而，脑转移患者需要加强综合管理。
